The objectives of this proposal are: 1) to test the hypothesis that survival of kidney and bone marrow grafts in humans is related to the response of recipients to hepatitis B infection before transplantation; 2) to gain insight into the mechanism by which responses to hepatitis B virus might be related to responses to organ grafts. Specifically, to test the hypothesis that there is cross reactivity between antigenic determinants on HBV and a male-associated antigen. Studies of first kidney transplants in 197 recipients show that grafts from male donors in anti-HBs (plus) female recipients have a poorer survival (approximately 65% survival at 15 months). These difference are not explaaned by other factors (HLA matching, relatedness of donor and recipient, transfusions, etc.) known to affect graft survival. Analysis of sibling bone marrow graft in 72 patients with aplastic anemia revealed very poor patient survial (2 of 18) in both anti HBs (plus) and anti HBs (plus) female recipients of grafts from their brothers. Assays of cross reactivity between anti-HBs and antisperm antibodies are in progress.